Resting-state Functional Connectivity In Patients Research Articles

Acupuncture modulates emotional network resting-state functional connectivity in patients with insomnia disorder: a randomized controlled trial and fMRI study

BackgroundInsomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia.MethodsA total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation.ResultsResting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p < 0.05, FDR corrected). In real acupuncture group, the rsFC value was decreased between left amygdala and left thalamus after 4 weeks of treatment compared with baseline. A trend of correlation was found that the increased rsFC value between the right amygdala and left hippocampus was positively correlated with the decreased HAMA scores across all ID patients, and the decreased left amygdala rsFC value with the left thalamus was negatively correlated with the increased sleep efficiency in the real acupuncture group.ConclusionOur findings showed that real acupuncture could produce a positive effect on modulating rsFC within network related to emotion processing in ID patients, which may illustrate the central mechanism underlying acupuncture for insomnia in improving sleep quality and emotion regulation.Trial registrationhttp://www.chictr.org.cn., ChiCTR1800015282, 20/03/2018.

Specific alterations of resting-state functional connectivity in the triple network related to comorbid anxiety in major depressive disorder.

The brain's default mode network (DMN) and the executive control network (ECN) switch engagement are influenced by the ventral attention network (VAN). Alterations in resting-state functional connectivity (RSFC) within this so-called triple network have been demonstrated in patients with major depressive disorder (MDD) or anxiety disorders (ADs). This study investigated alterations in the RSFC in patients with comorbid MDD and ADs to better understand the pathophysiology of this prevalent group of patients. Sixty-eight participants (52.9% male, mean age 35.3years), consisting of 25 patients with comorbid MDD and ADs (MDD + AD), 20 patients with MDD only (MDD) and 23 healthy controls (HCs) were investigated clinically and with 3T resting-state fMRI. RSFC utilizing a seed-based approach within the three networks belonging to the triple network was compared between the groups. Compared with HC, MDD + AD showed significantly reduced RSFC between the ECN and the VAN, the DMN and the VAN and within the ECN. No differences could be found for the MDD group compared with both other groups. Furthermore, symptom severity and medication status did not affect RSFC values. The results of this study show a distinct set of alterations of RSFC for patients with comorbid MDD and AD compared with HCs. This set of dysfunctions might be related to less adequate switching between the DMN and the ECN as well as poorer functioning of the ECN. This might contribute to additional difficulties in engaging and utilizing consciously controlled emotional regulation strategies.

An examination of resting-state functional connectivity in patients with active Crohn's disease.

Alterations in resting state functional connectivity (rs-FC) in Crohn's Disease (CD) have been documented in default mode network (DMN) and frontal parietal network (FPN) areas, visual, cerebellar, salience and attention resting-state-networks (RSNs), constituting a CD specific neural phenotype. To date, most studies are in patients in remission, with limited studies in active disease. Twenty five active CD cases and 25 age-, BMI- and gender-matched healthy controls (HC) were recruited to a resting-state-functional Magnetic Resonance Imaging (rs-fMRI) study. Active disease was defined as C-reactive protein>5 mg/dL, faecal calprotectin>250 μg/g, or through ileocolonoscopy or MRE. rs-fMRI data were analysed using independent component analysis (ICA) and dual regression. Differences in RSNs between HCs and active CD were assessed, and rs-FC was associated with disease duration and abdominal pain. Increased connectivity in the FPN (fusiform gyrus, thalamus, caudate, posterior cingulate cortex, postcentral gyrus) and visual RSN (orbital frontal cortex) were observed in CD versus HC. Decreased activity was observed in the salience network (cerebellum, postcentral gyrus), DMN (parahippocampal gyrus, cerebellum), and cerebellar network (occipital fusiform gyrus, cerebellum) in CD versus HCs. Greater abdominal pain scores were associated with lower connectivity in the precuneus (visual network) and parietal operculum (salience network), and higher connectivity in the cerebellum (frontal network). Greater disease duration was associated with greater connectivity in the middle temporal gyrus and planum temporale (visual network). Alterations in rs-FC in active CD in RSNs implicated in cognition, attention, emotion, and pain may represent neural correlates of chronic systemic inflammation, abdominal pain, disease duration, and severity.

Altered Large-Scale Resting-State Functional Network Connectivity in Convergence Insufficiency Young Adults Compared With Binocularly Normal Controls.

To investigate the underlying resting-state functional connectivity (RSFC) of symptomatic convergence insufficiency (CI) compared with binocularly normal controls (BNC) using functional magnetic resonance imaging (fMRI) under The Convergence Insufficiency Neuro‑mechanism Adult Population Study (NCT03593031). A total of 101 participants were eligible for this study. After removing datasets with motion artifacts, 49 CI and 47 BNC resting-state functional magnetic resonance imaging datasets were analyzed. CI was diagnosed with the following signs: (1) receded near point of convergence of 6 cm or greater, (2) decreased positive fusional vergence of less than 15∆ or failing Sheard's criteria of twice the near phoria, (3) near phoria of at least 4∆ more exophoric compared with the distance phoria, and (4) symptoms using the Convergence Insufficiency Symptom Survey (score of ≥21). RSFC was assessed using a group-level independent components analysis and dual regression. A behavioral correlation analysis using linear regression method was performed between clinical measures and RSFC using the significant difference between the CI and BNC. On average, a decreased RSFC was observed within the frontoparietal network, default mode network and visual network in patients with CI, compared with the participants with BNC (P < 0.05, corrected for multiple comparisons). The default mode network RSFC strength was significantly correlated with the PFV, near point of convergence, and difference between the horizontal phoria at near compared with far (P < 0.05). Results support altered RSFC in patients with CI compared with participants with BNC and suggest that these differences in underlying neurophysiology may in part be in connection with the differences in optometric visual function used to diagnose CI.

Increased Resting-State Functional Connectivity in Patients With Autoimmune Addison Disease.

Individuals with autoimmune Addison disease (AAD) take replacement medication for the lack of adrenal-derived glucocorticoid (GC) and mineralocorticoid hormones from diagnosis. The brain is highly sensitive to these hormones, but the consequence of having AAD for brain health has not been widely addressed. The present study compared resting-state functional connectivity (rs-fc) of the brain between individuals with AAD and healthy controls. Fifty-seven patients with AAD (33 female) and 69 healthy controls (39 female), aged 19 to 43 years were scanned with 3-T magnetic resonance imaging (MRI). Independent component and subsequent dual regression analyses revealed that individuals with AAD had stronger rs-fc compared to controls in 3 networks: the bilateral orbitofrontal cortex (OFC), the left medial visual and left posterior default mode network. A higher GC replacement dose was associated with stronger rs-fc in a small part of the left OFC in patients. We did not find any clear associations between rs-fc and executive functions or mental fatigue. Our results suggest that having AAD affects the baseline functional organization of the brain and that current treatment strategies of AAD may be one risk factor.

Hypoconnectivity networks in schizophrenia patients: A voxel-wise meta-analysis of Rs-fMRI

BackgroundIn recent years several meta-analyses regarding resting-state functional connectivity in patients with schizophrenia have been published. The authors have used different data analysis techniques: regional homogeneity, seed-based data analysis, independent component analysis, and amplitude of low frequencies. Hence, we aim to perform a meta-analysis to identify connectivity networks with different activation patterns between people diagnosed with schizophrenia and healthy controls using voxel-wise analysis. Method: We collected primary studies exploring whole brain connectivity by functional magnetic resonance imaging at rest in patients with schizophrenia compared with healthy controls. We identified 25 studies included high-quality studies that included 1285 patients with schizophrenia and 1279 healthy controls. Results: The results indicate hypoactivation in the right precentral gyrus and the left superior temporal gyrus of patients with schizophrenia compared with healthy controls. Conclusions: These regions have been linked with some clinical symptoms usually present in Plea with schizophrenia, such as auditory verbal hallucinations, formal thought disorder, and the comprehension and production of gestures.

Resting-state functional connectivity in patients with minimally disabled Parkinson’s disease: A case-control study

Resting-state functional connectivity in patients with minimally disabled Parkinson’s disease: A case-control study

Altered resting-state functional connectivity within corticostriatal and subcortical-striatal circuits in chronic pain

Brain corticostriatal circuits are important for understanding chronic pain and highly relevant to motivation and cognitive processes. It has been demonstrated that in patients with chronic back pain, altered nucleus accumbens (NAcc)—medial prefrontal cortex (MPFC) circuit fMRI-based activity is predictive of patient outcome. We evaluated the NAcc-MPFC circuit in patients with another chronic pain condition, fibromyalgia, to extend these important findings. First, we compared fMRI-based NAcc-MPFC resting-state functional connectivity in patients with fibromyalgia (N = 32) vs. healthy controls (N = 37). Compared to controls, the NAcc-MPFC circuit’s connectivity was significantly reduced in fibromyalgia. In addition, within the fibromyalgia group, NAcc-MPFC connectivity was significantly correlated with trait anxiety. Our expanded connectivity analysis of the NAcc to subcortical brain regions showed reduced connectivity of the right NAcc with mesolimbic circuit regions (putamen, thalamus, and ventral pallidum) in fibromyalgia. Lastly, in an exploratory analysis comparing our fibromyalgia and healthy control cohorts to a separate publicly available dataset from patients with chronic back pain, we identified reduced NAcc-MPFC connectivity across both the patient groups with unique alterations in NAcc-mesolimbic connectivity. Together, expanding upon prior observed alterations in brain corticostriatal circuits, our results provide novel evidence of altered corticostriatal and mesolimbic circuits in chronic pain.

Altered cerebellar gray matter and cerebellar-cortex resting-state functional connectivity in patients with bipolar disorder Ⅰ

BackgroundBipolar disorder (BP) is a common psychiatric disorder characterized by extreme fluctuations in mood. Recent studies have indicated the involvement of cerebellum in the pathogenesis of BP. However, no study has focused on the precise role of cerebellum exclusively in patients with bipolar I disorder (BP-I). MethodsForty-five patients with BP-I and 40 healthy controls were recruited. All subjects underwent clinical evaluation and Magnetic Resonance diffusion Tension Imaging scans. For structural images, we used a spatially unbiased infratentorial template toolbox to isolate the cerebellum and then preformed voxel-based morphometry (VBM) analyses to assess the difference in cerebellar gray matter volume (GMV) between the two groups. For the functional images, we chose the clusters that survived from VBM analysis as seeds and performed functional connectivity (FC) analysis. Between-group differences were assessed using the independent Students t test or the nonparametric Mann‐Whitney U Test. For multiple comparisons, the results were further corrected with Gaussian random field (GRF) approach (voxel-level P < 0.001, cluster-level P < 0.05). ResultsCompared with healthy controls, BP-I patients showed significantly decreased GMV in left lobule V and left lobule VI (P < 0.05, GRF corrected). The FC of cerebellum with bilateral superior temporal gyrus, bilateral insula, bilateral rolandic operculum, right putamen, and left precentral gyrus was disrupted in BP-I patients (P < 0.05, GRF corrected). ConclusionsBP-I patients showed decreased cerebellar GMV and disrupted cerebellar-cortex resting-state FC. This suggests that cerebellar abnormalities may play an important role in the pathogenesis of BP-I.

Changes in resting-state functional connectivity in patients with congenital adrenal hyperplasia

ContextPatients with congenital adrenal hyperplasia (CAH) are treated with life-long glucocorticoid (GC) replacement therapy. Negative effects on cognition, brain structure and function during working memory tasks have been identified. To date, no studies on functional connectivity during rest have been performed in patients with CAH. ObjectiveTo investigate resting-state functional connectivity in patients with CAH compared with healthy untreated controls and the association between functional connectivity in the precuneus and disease severity, dose of GC and working memory (WM). Design, Setting and ParticipantsThirty-one patients with CAH (18 females) and 38 healthy controls (24 females), aged 16–33 years, from a single research institute, underwent functional magnetic resonance imaging of the brain during rest. ResultsPatients with CAH showed increased functional connectivity in the precuneus compared with controls. Post-hoc tests within the precuneus showed that only patients with simple virilising CAH had stronger connectivity compared to controls. Further, while both patients with salt-wasting and simple virilising CAH performed worse on a WM task compared to controls, functional connectivity in the precuneus was not associated with executive function performance. ConclusionPatients with CAH demonstrated altered functional connectivity during rest in the precuneus. Such a change may reflect a functional reorganisation in response to the CAH disease. The change in functional connectivity may depend on the severity of CAH.

Altered Static and Dynamic Interhemispheric Resting-State Functional Connectivity in Patients With Thyroid-Associated Ophthalmopathy.

Purpose: Thyroid-associated ophthalmopathy (TAO) is a debilitating and sight-threatening autoimmune disease that severely impairs patients’ quality of life. Besides the most common ophthalmic manifestations, the emotional and psychiatric disturbances are also usually observed in clinical settings. This study was to investigate the interhemispheric functional connectivity alterations in TAO patients using resting-state functional magnetic resonance imaging (rs-fMRI).Methods: Twenty-eight TAO patients and 22 healthy controls (HCs) underwent rs-fMRI scans. Static and dynamic voxel-mirrored homotopic connectivity (VMHC) values were calculated and compared between the two groups. A linear support vector machine (SVM) classifier was used to examine the performance of static and dynamic VMHC differences in distinguishing TAOs from HCs.Results: Compared with HCs, TAOs showed decreased static VMHC in lingual gyrus (LG)/calcarine (CAL), middle occipital gyrus, postcentral gyrus, superior parietal lobule, inferior parietal lobule, and precuneus. Meanwhile, TAOs demonstrated increased dynamic VMHC in orbitofrontal cortex (OFC). In TAOs, static VMHC in LG/CAL was positively correlated with visual acuity (r = 0.412, P = 0.036), whilst dynamic VMHC in OFC was positively correlated with Hamilton Anxiety Rating Scale (HARS) score (r = 0.397, P = 0.044) and Hamilton Depression Rating Scale (HDRS) score (r = 0.401, P = 0.042). The SVM model showed good performance in distinguishing TAOs from HCs (area under the curve, 0.971; average accuracy, 94%).Conclusion: TAO patients had altered static and dynamic VMHC in the occipital, parietal, and orbitofrontal areas, which could serve as neuroimaging prediction markers of TAO.

Clinical Effects of Repetitive Transcranial Magnetic Stimulation of the Motor Cortex Are Associated With Changes in Resting-State Functional Connectivity in Patients With Fibromyalgia Syndrome

In this double-blinded, sham-controlled, counterbalanced, and crossover study, we investigated the potential neuroplasticity underlying pain relief and daily function improvements following repetitive transcranial magnetic stimulation of the motor cortex (M1-rTMS) in fibromyalgia syndrome (FMS) patients. Specifically, we used magnetic resonance imaging (MRI) to examine changes in brain structural and resting-state functional connectivity (rsFC) that correlated with improvements in FMS symptomology following M1-rTMS. Twenty-seven women with FMS underwent real and sham treatment series, each consisting of 10 daily treatments of 10Hz M1-rTMS over 2 weeks, with a washout period in between. Before and after each series, participants underwent anatomical and resting-state functional MRI scans and questionnaire assessments of FMS-related clinical pain and functional and psychological burdens. The expected reductions in FMS-related symptomology following M1-rTMS occurred with the real treatment only and correlated with rsFC changes in brain areas associated with pain processing and modulation. Specifically, between the ventromedial prefrontal cortex and the M1 (t = -5.54, corrected P = .002), the amygdala and the posterior insula (t = 5.81, corrected P = .044), and the anterior and posterior insula (t = 6.01, corrected P = .029). Neither treatment significantly changed brain structure. Therefore, we provide the first evidence of an association between the acute clinical effects of M1-rTMS in FMS and functional alterations of brain areas that have a significant role in the experience of chronic pain. Structural changes could potentially occur over a more extended treatment period. PerspectiveWe show that the neurophysiological mechanism of the improvement in fibromyalgia symptoms following active, but not sham, rTMS applied to M1 involves changes in resting-state functional connectivity in sensory, affective and cognitive pain processing brain areas, thus substantiating the essence of fibromyalgia syndrome as a treatable brain-based disorder.

Characterization of Resting State Default Mode Network in Individuals with HbSS and HbSC, and Healthy Controls Using 7-Tesla Human MRI

Sickle cell disease (SCD) is complicated by accelerated brain aging and cerebrovascular complications leading to structural brain damage and altered resting state functional connectivity (RS-FC). Investigation of the Default Mode Network (DMN), the most studied of the RS-FC networks, by functional MRI may provide insight into the neurological and neuropsychiatric complications of SCD. Prior studies have largely focused on the HbSS genotype of SCD as opposed to the HbSC genotype, which accounts for 30% of the total SCD cases in the US. Both genotypes are expected to impact brain disease, but in different manner.The aim of this study was to characterize the DMN in patients with HbSC, HbSS and healthy race and age-matched controls using state of the art 7-Tesla (7T) magnetic resonance imaging (MRI) with high contrast- and signal- to-noise ratios. On the day of the MRI scanning, participants were administered the brief pain inventory questionnaire (BPI), the digit symbol substitution test of cognitive function, and underwent basic blood work. Controls (n= 43, 53% female, mean age = 36+/-12 years), patients with HbSS (n=19, 63% female, mean age= 36+/-12) and HbSC (n=16 (50% female, mean age=36+/-13) were scanned using a 7T Siemens Magnetom scanner with the Tic Tac Toe radiofrequency coil system (Ibrahim et al., 2013). We obtained whole brain structural T1-weighted images and blood oxygenations level dependent resting state functional MRI (RS-fMRI). During the RS-fMRI, participants were instructed to keep their eyes open, look at a fixation cross, and lie without motion in the scanner. To identify significant differences in RS-FC between the groups, we conducted voxel-wise nonparametric analysis of variance. In the cortical areas with significant clusters, we ran ad-hoc t-tests (controls vs. HbSS, HbSC vs. HbSS, 1000 permutations, uncorrected cluster forming threshold = p < 0.001, family-wise error (FWE) rate=0.05) and we added age and sex as confounders. Then, we correlated RS-FC and the following variables: age, hemoglobin, BPI total, and DSST score.We found a significant difference between the three groups in the DMN (Fig 1) (p=0.0002). The ad-hoc t-tests showed that in the DMN, the RS-FC for the medial prefrontal cortex (mPFC) was significantly higher for the controls when compared to patients with HbSS (p=0.002). RS-FC for the mPFC was also significantly higher in patients with HbSC as compared to HbSS (p=0.001). There was a non-significant trend towards lower RS-FC in patients with HbSC as compared to controls. We also found weak non-significant negative correlation, (r= -0.24, p=0.1315), a strong significant negative correlation (r=-0.5, p=0.04) and very strong significant negative correlation (r=-0.8, p=0.001) between age and RS-FC in the mPFC for controls, HbSC, and HbSS patients, respectively. (Fig 2). We did not find any significant correlation between the RS-FC in the three groups and Hb levels, BPI total, and DSST score.In this work and for the first time, using 7T human MRI we identified altered RS-FC between SCD genotypes and between controls and patients with HbSS. It is notable that the RS-FC for HbSC patients was intermediate between that of the other two groups. Our results imply the RS-FC levels might be susceptible to disease genotype and not necessarily Hb levels, cognition and pain. The finding of a stronger correlation between age and FC in patients with SCD as compared to controls corroborates the notion that accelerated brain aging is operant in SCD. [Display omitted] DisclosuresNovelli: Novartis Pharmaceuticals: Consultancy.

Altered empathy-related resting-state functional connectivity in patients with bipolar disorder.

Empathy is the ability to generate emotional responses (i.e., cognitive empathy) and to make cognitive inferences (i.e., affective empathy) to other people's emotions. Empirical evidence suggests that patients with bipolar disorder (BD) exhibit impairment in cognitive empathy, but findings on affective empathy are inconsistent. Few studies have examined the neural mechanisms of cognitive and affective empathy in patients with BD. In this study, we examined the empathy-related resting-state functional connectivity (rsFC) in BD patients. Thirty-seven patients with BD and 42 healthy controls completed the self-report Questionnaires of Cognitive and Affective Empathy (QCAE), the Yoni behavioural task, and resting-sate fMRI brain scans. Group comparison of empathic ability was conducted. The interactions between group and empathic ability on seed-based whole brain rsFC were examined. BD patients scored lower on the Online Simulation subscale of the QCAE and showed positive correlations between cognitive empathy and the rsFC of the dorsal Medial Prefrontal Cortex (dmPFC) with the lingual gyrus. The correlations between cognitive empathy and the rsFC of the temporal-parietal junction (TPJ) with the fusiform gyrus, the cerebellum and the parahippocampus were weaker in BD patients than that in healthy controls. These findings highlight the underlying neural mechanisms of empathy impairments in BD patients.

Discriminating Suicide Attempters and Predicting Suicide Risk Using Altered Frontolimbic Resting-State Functional Connectivity in Patients With Bipolar II Disorder.

Bipolar II disorder (BD-II) major depression episode is highly associated with suicidality, and objective neural biomarkers could be key elements to assist in early prevention and intervention. This study aimed to integrate altered brain functionality in the frontolimbic system and machine learning techniques to classify suicidal BD-II patients and predict suicidality risk at the individual level. A cohort of 169 participants were enrolled, including 43 BD-II depression patients with at least one suicide attempt during a current depressive episode (SA), 62 BD-II depression patients without a history of attempted suicide (NSA), and 64 demographically matched healthy controls (HCs). We compared resting-state functional connectivity (rsFC) in the frontolimbic system among the three groups and explored the correlation between abnormal rsFCs and the level of suicide risk (assessed using the Nurses' Global Assessment of Suicide Risk, NGASR) in SA patients. Then, we applied support vector machines (SVMs) to classify SA vs. NSA in BD-II patients and predicted the risk of suicidality. SA patients showed significantly decreased frontolimbic rsFCs compared to NSA patients. The left amygdala-right middle frontal gyrus (orbital part) rsFC was negatively correlated with NGASR in the SA group, but not the severity of depressive or anxiety symptoms. Using frontolimbic rsFCs as features, the SVMs obtained an overall 84% classification accuracy in distinguishing SA and NSA. A significant correlation was observed between the SVMs-predicted NGASR and clinical assessed NGASR (r = 0.51, p = 0.001). Our results demonstrated that decreased rsFCs in the frontolimbic system might be critical objective features of suicidality in BD-II patients, and could be useful for objective prediction of suicidality risk in individuals.

Effects of High-Definition Transcranial Direct-Current Stimulation on Resting-State Functional Connectivity in Patients With Disorders of Consciousness.

Recently a positive treatment effect on disorders of consciousness (DOCs) with high-definition transcranial direct-current stimulation (HD-tDCS) has been reported; however, the neural modulation mechanisms of this treatment’s efficacy need further investigation. To better understand the processing of HD-tDCS interventions, a long-lasting HD-tDCS protocol was applied to 15 unresponsive wakefulness syndrome (UWS) patients and 20 minimally conscious states (MCS) patients in this study. Ten minutes of resting-state electroencephalograms (EEGs) were recorded from the patients, and the coma recovery scale-revised scores (CRS-Rs) were assessed for each patient from four time-points (T0, T1, T2, and T3). Brain networks were constructed by calculating the EEG spectral connectivity using the debiased weighted phase lag index (dwPLI) and then quantified the network information transmission efficiency by graph theory. We found that there was an increasing trend in local and global information processing of beta and gamma bands in resting-state functional brain networks during the 14 days of HD-tDCS modulation for MCS patients. Furthermore, the increased functional connectivity not only occurred in the local brain area surrounding the stimulation position but was also present across more global brain areas. Our results suggest that long-lasting HD-tDCS on the precuneus may facilitate information processing among neural populations in MCS patients.

Decreased Hand Motor Resting-State Functional Connectivity in Patients with Glioma: Analysis of Factors including Neurovascular Uncoupling.

Background Resting-state functional MRI holds substantial potential for clinical application, but limitations exist in current understanding of how tumors exert local effects on resting-state functional MRI readings. Purpose To investigate the association between tumors, tumor characteristics, and changes in resting-state connectivity, to explore neurovascular uncoupling as a mechanism underlying these changes, and to evaluate seeding methodologies as a clinical tool. Materials and Methods Institutional review board approval was obtained for this HIPAA-compliant observational retrospective study of patients with glioma who underwent MRI and resting-state functional MRI between January 2016 and July 2017. Interhemispheric symmetry of connectivity was assessed in the hand motor region, incorporating tumor position, perfusion, grade, and connectivity generated from seed-based correlation. Statistical analysis was performed by using one-tailed t tests, Wilcoxon rank sum tests, one-way analysis of variance, Pearson correlation, and Spearman rank correlation, with significance at P < .05. Results Data in a total of 45 patients with glioma (mean age, 51.3 years ± 14.3 [standard deviation]) were compared with those in 10 healthy control subjects (mean age, 50.3 years ± 17.2). Patients showed loss of symmetry in measures of hand motor resting-state connectivity compared with control subjects (P < .05). Tumor distance from the ipsilateral hand motor (IHM) region correlated with the degree (R = 0.38, P = .01) and strength (R = 0.33, P = .03) of resting-state connectivity. In patients with World Health Organization grade IV glioblastomas 40 mm or less from the IHM region, loss of symmetry in strength of resting-state connectivity was correlated with tumor perfusion (R = 0.74, P < .01). In patients with gliomas 40 mm or less from the IHM region, seeding the nontumor hemisphere yielded less asymmetric hand motor resting-state connectivity than seeding the tumor hemisphere (connectivity seeded:contralateral = 1.34 nontumor vs 1.38 tumor hemisphere seeded; P = .03, false discovery rate threshold = 0.01). Conclusion Hand motor resting-state connectivity was less symmetrical in a tumor distance-dependent manner in patients with glioma. Differences in resting-state connectivity may be false-negative results driven by a neurovascular uncoupling mechanism. Seeding from the nontumor hemisphere may attenuate asymmetry in patients with tumors near ipsilateral hand motor cortices. © RSNA, 2020 Online supplemental material is available for this article.

The Effect of Transcranial Direct Current Stimulation in Changing Resting-State Functional Connectivity in Patients With Neurological Disorders: A Systematic Review

Background:People with neurological disorders are found to have abnormal resting-state functional connectivity (rsFC), which is associated with the persistent functional impairment found in these patients. Recently, transcranial direct current stimulation (tDCS) has been shown to improve rsFC, although the results are inconsistent.Objective:We hope to explore whether tDCS induces rsFC changes among patients with neurological disorders, whether rsFC is clinically relevant and how different tDCS parameters affect rsFC outcome among these individuals.Methods:A systematic review was conducted according to PRISMA guidelines (systematic review registration number: CRD42020168654). Randomized controlled trials that studied the tDCS effects on rsFC between the experimental and sham-controlled groups using either electrophysiological or neuroimaging methods were included.Results:Active tDCS can induce changes in both localized (ie, brain regions under the transcranial electrodes) and diffused (ie, brain regions not directly influenced by the transcranial electrodes) rsFC. Interestingly, fMRI studies showed that the default mode network was enhanced regardless of patients’ diagnoses, the stimulation paradigms used or the rsFC analytical methods employed. Second, stimulation intensity, but not total stimulation time, appeared to positively influence the effect of tDCS on rsFC.Limitations and conclusion:Due to the inherent heterogeneity in rsFC analytical methods and tDCS protocols, meta-analysis was not conducted. We recommend that future studies may investigate the effect of tDCS on rsFC for repeated cathodal stimulation. For clinicians, we suggest anodal stimulation at a higher stimulation intensity within the safety limit may maximize tDCS effects in modulating aberrant functional connectivity of patients with neurological disorders.

Dysregulation of resting-state functional connectivity in patients with Cushing's disease.

To explore the anatomical distance-dependent functional connectivity patterns in patients with active phase of Cushing's disease (CD) and to evaluate the associations between hypercortisol exposure and regional normalized functional connectivity strengths (nFCSs). Based on the fMRI data in 32 CD patients and 32 healthy controls (HCs), we computed the nFCSs for each voxel in the brain and further divided them into long-range and short-range nFCSs. General linear models was used to investigate between-group differences in these nFCS metrics and the correlations between the nFCSs and clinical variables. Compared with HC, CD patients showed dysregulation of the nFCSs mainly in the default mode network. They showed an overall higher nFCS in bilateral parahippocampal cortex mainly owing to the disruption of long-range nFCS and a relatively lower nFCS in bilateral posterior cingulate cortex (PCC), bilateral lateral parietal cortex (LP), and right prefrontal cortex (PFC). In addition, their long-range nFCS was lower in the bilateral anterior cingulate cortex, PCC, and LP; short-range nFCS was lower in the bilateral PFC. Notably, the positive correlation between the nFCSs in their right parahippocampal cortex and serum cortisol levels at 08:00 remained significant after taking the anatomical distance into consideration. The discrepant functional connectivity patterns found in our study indicated a hypercortisol-associated, distance-dependent disruption of resting-state functional connectivity in patients with active CD. We provide novel insights into the impacts of hypercortisol exposure and the pathophysiologic mechanisms of CD, which may facilitate advances in CD intervention ultimately.

Alterations in resting-state functional connectivity in patients with Crohn\u2019s disease in remission

Previous studies have found neural alterations in regions involved in cognitive and affective functions among Crohn’s disease (CD) patients. The present work recruited 18 CD patients and 18 age-gender matched healthy controls (HC) and specifically compared differences in resting-state functional connectivity (RSFC) within the executive control network (ECN) which has been implicated in cognitive function and default mode network (DMN), which has been implicated in affective function. Additionally, we examined the correlations between RSFC in ECN and verbal fluency (VF) in both groups as well as RSFC in DMN and anxiety level in the CD group. Results showed significantly increased RSFC between the right middle frontal gyrus and right inferior parietal lobule in ECN, as well as increased RSFC between the right precuneus and right posterior cingulate cortex in DMN, among CD patients compared to HC. However, the correlations between ECN/DMN and behavioral scores in each group were not significant, which was possibility due to the limited sample size. These findings suggest that CD patients may experience changes in the connectivity patterns in ECN and DMN. Increased connectivity observed on these networks could be a potential biomarker of a neuropsychiatric manifestation of CD.